The mechanism of cell lysis by cytotoxic T lymphocytes (CTL) has been examined using both rabbit and mouse CTL. A standard murine (CBA or BALB/c anti-EL4) CTL system was used to demonstrate that cell surface thiols and proteases were necessary for CTL function (Redelman and Hudig, J. Immunol., 124, in press, 1980). Concurrently, a rabbit anti-mouse CTL system was developed to take advantage of the unique Ig VH allotype system of the rabbit that would allow one to identify receptor framework determinants. Rabbit cytotoxic effector cells were generated by culturing rabbit lymphoid cells from the spleen, mesenteric lymph nodes (MLN) or peripheral blood (PBL) with mitomycin-treated mouse stimulators for 4-7 days. These cytotoxic cells had the following properties of CTL: Rabbit T cells were necessary and sufficient for their generation, the effector cells could distinguish between targets of different inbred mouse strains including congenics differing only at H-2, both tumor and normal mitogen-stimulated blasts could be lysed and lysis was not inhibited by aggregated Ig. The generation of these CTL could be modulated by cells with properties resembling B and/or plasma cells (Russell and Redelman, Fed. Proc., 38, 1016, 1979). Lysis by these CTL could also be inhibited by specific anti-T cell serum (ATS) in the absence of exogenous complement (Redelman and Trefts, J. Immunol., 121, 1532, 1978). Future experiments will seek to determine whether rabbit CTL express Ig VH determinants and the identity of the functional molecule(s) recognized by ATS. It is possible that the ATS may inhibit by interfering with molecules analagous to those with thiols and/or protease activity that were demonstrated in the mouse CTL system.